Studies on cytostatic antitumor mechanism by a new PI3K inhibitor ZSTK474

新型PI3K抑制剂ZSTK474的细胞抑制抗肿瘤机制研究

• 批准号: 20790087
• 负责人: DAN Shingo
• 金额: $ 2.83万
• 依托单位: Japanese Foundation For Cancer Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790087/
• 关键词: PI3K; DNAチップ; 細胞周期; アポトーシス; 抗がん剤

We demonstrated that PI3K inhibitors including ZSTK474 did not induce apoptosis but G_0/G_1 arrest of cell cycle in cancer cell lines with PIK3CA/PTEN aberrations in vitro. In parallel, PI3K inhibitors exhibited their antitumor effect without inducing apoptosis in vivo. We examined gene expression changes after treatment of cancer cells with ZSTK474 by using GeneChip, and found induction of CDK inhibitor p15 and repression of CDC25A after ZSTK474 treatment. These changes would be involved in G_0/G_1 arrest of cell cycle.

我们在体外实验中发现，包括ZSTK 474在内的PI 3 K抑制剂不能诱导PIK 3CA/PTEN异常的癌细胞凋亡，但能使细胞周期阻滞于G_0/G_1期。同时，PI 3 K抑制剂在体内表现出其抗肿瘤作用而不诱导细胞凋亡。我们用基因芯片检测了ZSTK 474处理癌细胞后基因表达的变化，发现ZSTK 474处理后诱导CDK抑制剂p15和抑制CDC 25 A。这些变化可能与细胞周期G_0/G_1期阻滞有关。

项目成果

ZSTK47, a novel PI3K infibitor, down-regulates CDC25A and induces G1 phase cell cycle arrest in fuman cancer cells.

ZSTK47 是一种新型 PI3K 抑制剂，可下调 CDC25A 并诱导福曼癌细胞 G1 期细胞周期停滞。

• 发表时间: 2008
• 作者: Dan S;Mukai Y;YaguchiS;Yamori T.
• 通讯作者: Yamori T.

Inhibition of PI3K by ZSTK474 suppressed tumor growth not via apoptosis but GO/G1 arrest.

ZSTK474 对 PI3K 的抑制不是通过细胞凋亡而是通过 GO/G1 停滞来抑制肿瘤生长。

• 发表时间: 2009
• 期刊: Biochemical and biophysical research communications 379
• 作者: Dan S;Yoshimi H;Okamura M;Mukai Y;Yamori T.
• 通讯作者: Yamori T.

Correlation between efficacy of PI3K inhibitors and aberration of PI3K3 CA/PTEN in a panel of 39 human cancer cell lines(JFCR39)

39 种人类癌细胞系 (JFCR39) 中 PI3K 抑制剂的功效与 PI3K3 CA/PTEN 畸变之间的相关性

• 发表时间: 2010
• 作者: Dan S;Sugita H;Seki M;Mukai Y;Yamazaki K;Ishikawa Y;Yamori T.
• 通讯作者: Yamori T.

Inhibition profiles of phosphatidylinositol 3-kinase inhibitors against PI3K superfamily and human cancer cell line panel JFCR39

• DOI: 10.1016/j.ejca.2010.01.005
• 发表时间: 2010-04-01
• 期刊: EUROPEAN JOURNAL OF CANCER
• 影响因子: 8.4
• 作者: Kong, Dexin;Dan, Shingo;Yamori, Takao
• 通讯作者: Yamori, Takao

Correlating PI3K inhibitor efficacy with signaling pathway status : in silico and biological evaluations

将 PI3K 抑制剂功效与信号通路状态相关联：计算机和生物学评估

• 发表时间: 2010
• 期刊: Cancer Res (in press)
• 作者: Dan S;Okamura M;Seki M;Yamazaki K;Sugita H;Okui M;Mukai Y;Nishimura H;Asaka R;Nomura K;Ishikawa Y;Yamori T.
• 通讯作者: Yamori T.